C. difficile is a gram-positive, spore forming anaerobic bacterium that is the primary causative agent for pseudomembranous colitis and bacterial-induced diarrhea. C. difficile is rapidly emerging as a nosocomial pathogen in health care facilities around the world with an estimated 1 to 3% of all hospitalized patients under antibiotic treatment becoming infected with C. difficile. Even more alarming, a recent outbreak of a more virulent strain of C. difficile was correlated with the death of more than 100 patients within a 6-month period in a single hospital.
In the U.S., Clostridium difficile infection (CDI) is one of the most prolific causes of bacterial-induced diarrhea. Up to 3 million cases are estimated annually at a cost greater than $3.5 billion, with infection rates in some hospitals approaching 40%. In the last 15 years, the incidence of CDI has more than doubled. This increase is largely due to the emergence of a new hypervirulent strain (BI/NAP1/027) that releases pathogenic exotoxins, causing colonic inflammation and fluid secretion. Despite a known correlation between antimicrobial disruption of protective gut microflora and the development of symptoms in infected individuals, there is still a major gap in our understanding of why certain patients are susceptible to disease by this pathogen. Readily available treatment options for CDI include metronidazole and vancomycin, but both drugs are associated with relapse rates as high as 35%. Disease recurrence increases further (up to approximately 50%) in subsequent infective episodes, often necessitating surgical intervention. Thus, disease relapse represents the most significant clinical issue in CDI, and there is an urgent need to identify and prophylactically manage high-risk patients.
Given the complex genetic, proteomic, and environmental interactions that appear to be involved in CDI there is a need to develop a comprehensive categorization of subjects based on molecular and phenotypic variables. More specifically, there is a need to categorize functional metabolites in patient samples as biomarkers of clinical phenotype, activity, and treatment.